The overall objectives of this project are to investigate the physicochemical properties of polymers of sickle cell hemoglobin in order to obtain information that may be helpful in the ultimate goal of significantly inhibiting polymerization. The architectural aspects of unliganded Hb S polymers are being investigated by X-ray diffraction techniques. One of the major obstacles encountered in obtaining such informaton is the lack of parallel alignment of the polymers. Recently acquired techniques in handling erythrocytes have improved polymer alignment and consequently the resolution of the X-ray diffraction patterns. It is particularly important that the resolution of the diffraction patterns of packed sickled erythroctyes are comparable to the resolution observed in some instances in the patterns obtained from cell-free polymers. Thus information about polymeric architecture can be obtained directly from sickled erythrocytes. For the first time parallel alignment of this extent is systematically reproducible. Calculated diffraction patterns of polymer models will be compared with observed diffraction patterns in order to ultimately determine the intermolecular interactions within the polymers. Additional experiments exploring critical concentrations for polymerization of unliganded or partially liganded sickle hemoglobin under conditions encountered in the circulation of the erythrocytes are in progress.